Reference: Brion C, et al. (2020) Simultaneous quantification of mRNA and protein in single cells reveals post-transcriptional effects of genetic variation. Elife 9

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Abstract


Trans-acting DNA variants may specifically affect mRNA or protein levels of genes located throughout the genome. However, prior work compared trans-acting loci mapped in separate studies, many of which had limited statistical power. Here, we developed a CRISPR-based system for simultaneous quantification of mRNA and protein of a given gene via dual fluorescent reporters in single, live cells of the yeast Saccharomyces cerevisiae. In large populations of recombinant cells from a cross between two genetically divergent strains, we mapped 86 trans-acting loci affecting the expression of ten genes. Less than 20% of these loci had concordant effects on mRNA and protein of the same gene. Most loci influenced protein but not mRNA of a given gene. One locus harbored a premature stop variant in the YAK1 kinase gene that had specific effects on protein or mRNA of dozens of genes. These results demonstrate complex, post-transcriptional genetic effects on gene expression.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Brion C, Lutz SM, Albert FW
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